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Patients Speak: Choosing Focal Therapy

Mr. David Fitch talks to Prostatepedia about choosing focal therapy for prostate cancer.

Join us to read our November issue on focal therapy.

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What was your life like before prostate cancer?

Mr. David Fitch: I live by myself. I’m 74. I’m retired. Ever since I quit working, I found it is a lot better to interact with my friends. I bicycle and swim. I’m more of a cyclist than a swimmer. I cycle almost every day. I’m probably riding 200 to 300 miles a week. I started doing that initially for the social part of it—all my friends are bicycle folks.

Then I got into the VA Palo Alto swimming pool a few years ago and so I’ve got a lot of VA pals as well. All my exercise basically started as more of a social thing. That’s what was happening before the diagnosis of prostate cancer.

How did you find out that you had prostate cancer?

Mr. Fitch: That was through the VA. The VA in Palo Alto, California, is really good. I’ve been going there for over 10 years. I found out through my endocrinologist. I can’t say enough nice things about her. She has literally saved my life at least twice and this was one of those times. She was looking at my PSA over the years. She said: “It’s gently rising. It doesn’t really rise to the threshold of being something to worry about.” It was around 2.5 for several years before rising to around 3.5 over a period of about four to five years. She said, “Would you like to go talk to the urology department?” I said, “Sure, I’m always happy to talk to people.” She sent me to the head of the urology department. I had no clue about what a urologist did. I went to see the guy, and he did a digital rectal exam (DRE) and said he could feel a lump. My previous DRE was 18 months earlier with my primary care physician and she said everything was fine.

The urologist sent me for an MRI— I had no idea what an MRI was. This started my research: What’s an MRI? With the MRI he said, “It looks to me like there’s something wrong, so I need to do a biopsy.” He told me that the protocol for the VA is a blind biopsy, not using the MRI, just poking 12 holes or so into my prostate and taking samples. Very hit-or-miss. My research indicated that using the MRI fused to a picture of my prostate gave the radiologist a better chance of seeing the suspicious areas to sample, but the VA doesn’t do that. There is a program, Veteran’s Choice, that allows patients to be sent outside the VA if a procedure cannot be performed within the VA. I was sent to Stanford for an MRI-ultrasound fusion biopsy. The Stanford radiologist, Dr. Sonn, found lesions on both sides of my prostate. The right side had more suspicious areas than the left. The pathologist’s report confirmed the presence of intermediate prostate cancer. On the right side were two areas: Gleason 4+3 and 3+4. On the left side, it was Gleason 3+4.

What was your reaction? How did you feel when you found this out?

Mr. Fitch: I was very concerned of course but not distraught. The VA Urology Department did not inform me of the difference between blind biopsy and directed biopsy or of the availability of the Veteran’s Choice Program until I asked. I was now suspicious: What else hadn’t I been told? The only solution was my own research. I went down this rabbit hole trying to answer: What is prostate cancer? What does it mean? What do all these numbers mean? Who can do what, and how do I go about finding out? I joined a support group at the VA Palo Alto, which was worthless. Then I went to two other local support groups, one in Los Gatos, and another at Mountain View—both of them pretty good.

I found out from talking to a lot of guys that doctors generally prescribe their own methods of taking care of this stuff, whether or not it fits. Urologists want to cut and radiologists want to radiate. Then I found an online support group, Inspire.com, a partner of Us TOO. It’s fairly comprehensive. You can get a lot of questions answered, and you can spend literally hundreds or thousands of hours digging through—it’s like trying to take a drink out of a fire hydrant.

I was willing to educate myself. I was looking for people who could help me educate myself to find out what needed to be done. The best way I can characterize this is the problem that I had didn’t seem to me to be life-threatening at the moment. It seemed to me like I had plenty of time to figure out what to do next, but I was going to have to do something.

I didn’t like the fact that the head of the VA Urology Department told me he could only offer me surgery or radiation—nothing else. I thought both of those things were like amputating my arm because I got a scratch. I told him that. I said, “You’re not helping me a whole lot.” I had a 20-minute appointment at most. He just seemed too busy to have any sort of a long conversation. I went in there with all this reference material, a ton of it. I didn’t exactly know where I wanted to go with it, but I wanted to have a conversation with the man. His bedside manner was terrible. He gave me 20 minutes and said, “Okay, well, do whatever you want.” I wasn’t getting anywhere.

At that point, I felt that the VA Urology Department was not very helpful. I began to realize that there is a huge difference in doctors’ expertise as far as prostate cancer was concerned. I realized that I had to take this into my own hands. I had to educate myself in order to be able to go forward: What is a urologist? A radiologist? An oncologist? Do they specialize in prostate cancer?

Later, after my focal laser ablation (FLA) procedure, I met Dr. John Leppert, a VA urologist who has been very helpful and supportive in my quest to understand prostate cancer.

Did you turn to the online groups? Is that where you went first for education?

Mr. Fitch: I started online, yes. I did a lot of reading. I just worked for a long time until I had the answers that I wanted. Additionally, I began to hear the names of certain doctors mentioned over and over again: Dr. Snuffy Myers, Dr. Mark Scholz, Dr. Mark Moyad, Dr. Fabio Almeida, Dr. Dan Sperling, Dr. Pete Carroll, Dr. Joe Busch, and many others.

In many cases, Google was where my investigation began and I watched many YouTube videos. I concluded that many doctors want to cut something out of me or to radiate me, and both those things have serious consequences. I didn’t like either one.

It was about that time that I stumbled onto FLA. It probably had more to do with side effects than it did with whether it worked or not, quite frankly. I found that the biggest side effect from FLA was financial. It would cost me $20,000.

I decided not to buy a new car that year and use the money to take care f my body instead. I’m being a little facetious here. If it didn’t work, I could always do anything I wanted to the second time around. That’s what led me to FLA.

Once you found out about focal therapy as an option, how did you figure out which form of focal therapy was best?

Mr. Fitch: My FLA was done in 2016. There are more types of focal therapies now than in 2015 when I made the decision. Additionally, there are very few doctors who do this particular FLA. I went to Dr. Eric Walser at the University of Texas Medical Branch in Galveston, who I think I found out about on Inspire.com. Initially, I was going to Dr. John Feller at Desert Medical Imaging in Indian Wells, California. He had a clinical trial that I was eligible for, but I changed my mind at the last minute because Dr. Feller’s clinical trial would cost more than Dr. Walser’s commercial practice and would require two trips. And Dr. Feller uses an MRI machine that is 1.5 Tesla. I know it works just fine in the right hands, but it is not a 3.0 Tesla machine.

What was the actual procedure like for you?

Mr. Fitch: The procedure was outpatient. It lasted maybe an hour. I was never knocked out. It was just local anesthetic. I spent a few days in Galveston recovering. They did two overlapping ablations on the right side and one on the left. They took larger margins to preclude missing some hard-to-see cancerous spots. Prior to this time, FLA procedures had recurrence rate in the 10-15% range. Taking a little larger margin around the tumor would reduce the recurrence rate. And in my case, they ablated twice, overlapping, on the right and once on the left side. The tumor on the left side was rather small and hard to see. The two tumors on the right side were fairly close to the urethra, which meant that when my poor old prostate swelled up from the ablation, it closed off the urethra. Without a catheter in place, I wouldn’t have been able to pee.

The only painful part of the procedure was reinsertion of the catheter for the blocked urethra. I ended up staying in Galveston from Monday to Friday waiting for the urethra to open. I was told this problem was not typical and was probably due to the ablation near the urethra.

Any side effects after the treatment?

Mr. Fitch: My ejaculations are dry. I’m told that’s pretty typical. I’m 74 years old and not having kids is really not a problem for me. Otherwise, there don’t seem to be any aftereffects.

How are you monitoring now for potential recurrence after treatment?

Mr. Fitch: Active surveillance. The protocol is to have a PSA test every three months and an MRI at six months and 12 months. If everything is clean at the end of 12 months, then maybe an MRI once a year. It varies a little bit after that. The PSAs typically go on at three-month intervals. They’re just part of my normal blood work that I have done at the VA.

To put the PSA in perspective, before the FLA, it was about 3.5. Three months after FLA, it dropped to 2.3. Then at six months, it dropped to 0.25. I was so surprised by that number that I had it confirmed with a second test a few days later. It was 0.28.

At nine months, it jumped back to 0.55. That could have been partly due to riding my bike a lot. That does have an impact on PSA. At one year post-FLA, it is 0.43. I’ve had a one-year MRI as well which shows some scarring but no other problems.

Do you have any advice for men who are in a similar situation?

Mr. Fitch: I would do it again for intermediate prostate cancer (i.e., Gleason 7) which has not metastasized. It’s expensive, not covered by insurance, and I had to travel, but it was well worth it. No pain, no leaking, and sex works. If the cancer reappears in the gland it can be re-ablated or any other procedure used. There are many available therapies for organ-contained prostate cancer that has not metastasized: cryotherapy, CyberKnife, MR-guided focused ultrasound, NanoKnife, proton beam, photodynamic therapy with TOOKAD, stereotactic body radiation therapy (SBRT), brachytherapy (seeds), and more. Technological improvements are happening quickly. I suspect we’re headed down the road of some new, permanent therapies that will eradicate prostate cancer forever. Immunotherapy comes to mind. Until then, FLA seems like a good interim measure.

Any other thoughts for other men struggling with prostate cancer?

Mr. Fitch: Listen to the doctors. If you like what they say, and if you want to follow their advice, that’s fine. If you think there might be something else out there that works better, at least take a look at other options and see how they stack up against what you’re being told. Prostate cancer probably hasn’t changed a heck of a lot in a long time, but the ways that we approach it are changing rapidly. Active surveillance for low-risk cancer (Gleason 6) is increasing dramatically, and scanning techniques make this possible. If it weren’t for the new technologies in scanning, we wouldn’t be doing focal anything. Scanning helps find the tumors. I was a fighter pilot. If somebody was shooting at me, I could combat that by seeing the threat and defeating it. The same goes here. If you can see it, you can probably defeat it.

There are a lot of scanning techniques including MRI. PET/CT scanning techniques use different imaging agents (injected during the scan) and can help to see both inside and outside the prostate. These agents include C 11-acetate, PSMA, Axumin (fluciclovine F 18), and many others. It’s worthwhile investigating those to make sure that a guy knows exactly what he’s got and exactly what he has to deal with before he goes down any road. He’s got lots of time, especially if it’s low or intermediate risk. Take the time to educate yourself, to understand what needs to be done.

The last point I’d make is to attend the Prostate Cancer Research Institute (PCRI) conferences in the fall. It’s designed for patients, given by world class doctors, lasts three days for $50 or so. The education is remarkable.

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Robotic Prostate Cancer Surgery After Focal Therapy

Dr. Paul Cathcart is a consultant urological surgeon at Guy’s Hospital and St. Thomas’ Hospital in London.

Prostatepedia spoke with him about a clinical trial he’s running that looks at robotic surgery in men whose prostate cancers have come back after focal therapy.

Why did you become a doctor?

Dr. Paul Cathcart: I always liked science; that was my favorite subject. I was thinking about whether to become a vet or a doctor and did lots of school visits. During one of those visits, I met an inspirational character, a surgeon. I spent some time with him, following him around hospital wards and clinics. I thought that he was the sort of person I would like to be: he does the job I’d like to do. I think that’s often the case in life: you meet some inspirational figure who pushes you along one line.

Later on, another inspirational figure who came into my life was a urologist. I was originally going to be a colorectal surgeon. Everything was set for that. Then I met this urologist who showed me the different mix there is in urology, which I found interesting. Then I met Dr. Mark Emberton; I was his research fellow for many years. He’s quite an inspirational person as well. I’ve been working with him for 17 years now on various things.

What is the thinking behind your trial on robotic surgery after focal ablation?

Dr. Cathcart: Focal therapy is a new concept, which Dr. Emberton and one or two other people have pioneered to reduce the side effects and morbidity of prostate cancer treatment. Unfortunately, a proportion of these patients will experience recurrent disease after focal therapy. No cancer treatment is 100% effective. A couple of these focal therapy patients were recurring three or four years after starting the focal therapy program.

No urologist wanted to operate on these patients because they felt that it would be an extremely difficult surgery. In fact, urologists were only offering exenterations to remove the patients’ prostate, bladder, etc.

I got to know quite a few of these patients. (I do a lot of post-radiotherapy surgery, as well.) I decided that this procedure called salvage surgery interested me. We thought that we could do this salvage surgery and maintain good outcomes for our patients because only part of their prostate had been treated during focal therapy. We thought that the side effects of the surgery after focal therapy would actually be a lot less than after radiation, but we needed evidence to prove it. That is why we set up the trial.

We’re also interested in learning why some patients may fail focal therapy. What is it about their disease that leads it to recur? If we can understand why some patients may fail focal therapy, this can help us select up front which patients should have focal therapy and which should not.

What can patients expect to happen during the trial?

Dr. Cathcart: We are halfway through the study at the moment.

Of course, patients undergo a salvage prostatectomy. We take the tissue to be analyzed and look for various genetic markers to see why their cancer may have returned.

This is also a toxicity and side effect study. We have patient-reported outcome measures at baseline and sequentially thereafter. There are a number of blood tests looking at hormone profiles before and after the surgery.

We follow patients for about 12 months after those sequential patient-reported outcome measures; we’re looking to chart that toxicity.

I’ve taken out more prostates after focal therapy than most because of my link with Dr. Emberton. We’re now demonstrating the feasibility and toxicity of salvage focal surgery and trying to understand why these tumors have recurred.

Are you still recruiting patients?

Dr. Cathcart: About 20 patients have undergone the surgery. We’re recruiting 20 more. We haven’t had any adverse events. We were worried about things like rectal injuries, because the rectum can stick to the prostate after focal therapy. We haven’t had any of those.

We’ve actually had a fantastic continence outcome. The prostate cancer community said everyone would be incontinent and impotent, but all our patients so far have been continent.

We’ve got the patient-reported outcome measures to demonstrate it.

The potency rates are taking a little bit longer to return to baseline. The outcomes from potency won’t be as good as the continence outcomes. We haven’t had any side effects at the time of surgery. No complications or anything, so we’re delighted with the way things have gone.

Does the fact that the man has had focal therapy make the potency issues worse?

Dr. Cathcart: It depends on the location of their focal treatment. In those with anterior tumors (tumors away from the neurovascular bundles), we’ve noticed potency returns faster. If they’ve had an ablation on the peripheral zone, near where one of the nerve bundles is located, potency returns more slowly.

We’re also noticing a difference between different treatments. You can give focal therapy with high-intensity focused ultrasound (HIFU), cryotherapy, or something called electroporation. The different energy sources have different effects on the structures surrounding the prostate and a different impact on the chance of potency returning. Electroporation seems to be very precise and leaves the least amount of collateral damage. In those patients, potency returns faster. Cryotherapy creates more periprostatic fibrosis and scarring; potency takes slightly longer for those patients to return. Potency return for HIFU patients falls somewhere in the middle of the modalities.

I’ve also taken out prostates after photodynamic therapy. Photodynamic therapy is better relative to preserving the tissue planes, but it does depend on which part of the prostate has been ablated in the first place.

Is there anything else you think patients should know about your trial?

Dr. Cathcart: We’re going to get a great understanding of why these patients in particular failed focal therapy. The genetic markers and the locations of the tumors will inform which patients are suitable for focal therapy from the beginning. There may be parts of the prostate, or particular types of tumors or genetic markers, which will identify patients best suited to a whole-gland approach such as a radical prostatectomy up front.

It’s not just about the location and grade of the tumor, but also about the tumor’s genetic signature, which may predispose a particular tumor to being better suited for focal therapy.

It’s interesting, in some patients you knock out one tumor say on the right-hand side and that’s it, the tumor never comes back. Other patients’ prostates seem somewhat unstable and have multiple tumors that keep appearing throughout the prostate. I’m sure there is a genetic basis to it.

Because we’re taking out these patients’ prostates, we can analyze all the different tumors. Some people even think that by treating part of the prostate we may be changing the genetics of that tumor—i.e., it gets angrier. I don’t think that’s the case. This study will help prove that point. We’re also going to open up a comparative arm of the study very soon for patients who have had whole-gland radiation or ablation techniques—open to anyone who has had the whole of their prostate treated with brachytherapy, radiotherapy, HIFU, or cryotherapy. We’ve been finding that patients who have had surgery following focal therapy have better outcomes than those who have had whole-gland therapy up front. We’re going to recruit into that second arm to demonstrate that surgery after focal therapy has a better outcome.

Can non-UK residents come to you for surgery?

I’ve got a clinic called the Recurrent Prostate Cancer Clinic. I have a reasonable number of patients who come from the United States. They normally come to Dr. Emberton for focal therapy, then if they develop recurrent disease, I operate on them. A lot of urologists wouldn’t operate on these patients. Certainly, in the United States, hardly anyone operates on post HIFU patients simply because HIFU has not been available until very recently.

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Imaging + Salvage Focal Therapy

Dr. R. Jeffrey Karnes is an Associate Professor and Vice Chair of the Urology Department at the Mayo Clinic in Rochester, Minnesota.

Prostatepedia spoke with him about how imaging impacts salvage focal therapy.

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How does newer imaging like gallium-68 PSMA PET/CT impact salvage focal therapy?

Dr. Karnes: PET imaging has been good at detecting metastases, but in terms of imaging the primary tumor, the resolution hasn’t been the best. Now, we and others are moving into a PET/MRI scan.

That is a fusion scan?

Dr. Karnes: A fusion scan with MRI rather than the PET/CT. Obviously, an MRI provides more resolution of the prostate. To me, MRI is obviously the gold standard when it comes to imaging the primary prostate. We’re certainly using the technology. Others are using it. We don’t really know what the exact accuracy is of the MRI/PET fusion scan in those who have had radiation failure.

And, as I mentioned, I don’t think we have really much in the way of a clue regarding the biology of this index lesion in radiation-recurrent cancer in the prostate. I think that in the glands of men who recur after radiation, there is probably higher tumor burden compared to the newly diagnosed patient.

A third problem we have when it comes to focal salvage therapy is that I don’t think we even have a great definition of what constitutes a potential local recurrence after primary radiation. The Phoenix definition used by the American Society for Radiation Oncology is the nadir (or lowest) PSA plus 2. This definition predicts recurrence, but what it really predicts is progression, not necessarily local recurrent disease.

In this country, for many men who fail radiation, the next treatment is hormonal therapy. Hormonal therapy really has only a palliative intent and won’t cure anyone of localized radiation-recurrent disease.

We need to do a better job of appropriately diagnosing radiation failure patients in the first place. What that better job would be, I don’t know. I don’t think routine biopsies, which have been looked at in the past, are the answer. But perhaps imaging sooner rather than waiting for the Phoenix definition makes sense. Maybe, as you mentioned appropriately, with the newer PET/MRI fusion scans, we can image men sooner to try to detect a local recurrent disease earlier.

That being said, I do a lot of salvage radical prostatectomies, almost one a week. This is unpublished, but I have not seen a big stage migration (less extraprostatic extension and/or nodal metastasis) in the last decade. I still see a lot of patients with radiation failure; they come to their salvage prostatectomy with seminal vesicle invasion and nodal disease. Up to a third of patients will have seminal vesicle invasion and I see nodal involvement in up to 20% at salvage surgery.

Why is that relevant to salvage focal therapy?

Dr. Karnes: A lot of the seminal vesicle invasion is not always evident on MRI. And a lot of these patients don’t get routine biopsies of their seminal vesicles. If they undergo a salvage focal therapy, their doctors are obviously going to be missing a significant component of their disease because salvage focal therapy, in my opinion, doesn’t work to ablate the seminal vesicles. Obviously, salvage focal therapy can do a job in the gland itself, but in the appendages, such as seminal vesicles, it is hard to get an appropriate ablation of the entire seminal vesicles because of the risk to adjacent structures— the bladder, the ureters, and so forth.

Another thought I have about salvage focal therapy is when we look at other forms of ablation technologies like cryotherapy or HIFU, we’ve morphed them from whole-gland to focal and now to focal salvage therapies. But I don’t think we even know who the ideal candidate is for whole-gland HIFU or whole-gland cryotherapy let alone the focal form of the therapies in a treatment-naïve patient. Obviously, these are alternatives or options for patients who are newly diagnosed, but more troubling for me is this: I don’t think we know exactly what constitutes a success. How do we monitor whole-gland cryotherapy or whole-gland HIFU? We’ve used PSA failure as a definition, but are we really using the right tool to monitor?

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Salvage Focal Therapy

Dr. R. Jeffrey Karnes is an Associate Professor and Vice Chair of the Urology Department at the Mayo Clinic in Rochester, Minnesota.

Prostatepedia spoke with him about salvage focal therapy for recurrent prostate cancer.

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What is focal therapy?

Dr. Karnes: Focal therapy is partial treatment of the prostate gland as opposed to whole-gland treatment (i.e., radical prostatectomy, brachytherapy, and photon or proton radiation therapy).

How did focal therapy even become in vogue? To abate some of the potential side effects of whole-gland treatment. It is exciting and promising, yet remains investigational.

Isn’t a focal approach common in other kinds of cancers?

Dr. Karnes: It can be. The most common is probably breast cancer. I’m far from an expert in breast cancer, but recurrence rates can be higher with focal therapy, meaning a lumpectomy or quadrantectomy, where a quadrant of the breast is removed. But, the survival has been similar between partial- vs. whole-breast treatment.

Why not the prostate? I would say that focal therapy, in general, hasn’t risen to the forefront in the United States or internationally. There are a couple of limitations for focal therapy in general:

1) What do we know about prostate imaging? Prostate cancer is known to be a multifocal cancer within the prostate. The multiparametric MRI is good. It’s not perfect. But even if we can identify a small focus of intermediate-grade prostate cancer, are we certain that is truly the disease to treat, as opposed to some scattered higher-grade cancer that may not be showing up on MRI, but hopefully might get picked up on a whole-gland biopsy done along with a targeted biopsy? I think we’re getting to the point where an MRI is pretty good at imaging the entire prostate.

2) We still have a second unresolved issue of what constitutes the biological index lesion of the cancer. If we do have multifocality, are we sure exactly which focus to treat? Even some of the well-known researchers in focal therapy (focal cryotherapy, high-intensity focused ultrasound [HIFU]) can still have patients with a fairly high recurrence, or persistence of the cancer after the partial or focal therapy about 20% of the time.

What is salvage focal therapy?

Dr. Karnes: Focal salvage therapy is focal therapy done when a man recurs after primary treatment. There is more at risk with focal salvage therapy. What do I mean by more at risk? Obviously, salvage therapy means that there has already been a primary treatment that has failed, so there is even more impetus to get it right the second time around. For that second time around, if we go back to those two items that I mentioned above (imaging and the biology of the index lesion), there has not been, to my mind, enough research into MRI imaging of recurrent prostate cancer. More research needs to be done into the MRI performance accuracy after a radiation.

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Active Surveillance V Partial-Gland Ablation

Dr. Behfar Ehdaie is a urologist at Memorial Sloan Kettering Cancer Center in New York City.

Prostatepedia spoke with him recently about active surveillance versus partial-gland ablation. Join us to read the entire conversation.

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Could low-risk patients just as easily choose active surveillance? Is it just patient choice: active surveillance or partial-gland ablation?

Dr. Ehdaie: I think active surveillance, partial-gland ablation, or focal therapy, and whole-gland treatments, which include radical retropubic prostatectomy or radiation therapy, exist on a spectrum for disease management in prostate cancer.

I do believe that there are patients who we would all agree are very good candidates for active surveillance. Men who’ve been diagnosed with Gleason 3+3 prostate cancer fall into this category. I think our discussion about men who may be eligible for focal therapy or partial-gland ablation would include men with intermediate risk prostate or Gleason 3+4 or 4+3 prostate cancer.

Of course, some of the men with low-volume Gleason 3+4 prostate cancer in foci within the prostate gland would also be considered very good candidates for active surveillance. It’s important that all patients are offered all treatments and that those treatments are explained in detail at every consultation.

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Focal Therapy Versus Partial-gland Ablation

Ehdaie_130821_14Dr. Behfar Ehdaie is a urologist at Memorial Sloan Kettering Cancer Center in New York City.

Prostatepedia spoke with him recently about focal therapy and laser ablation.

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Why did you become a doctor?

Dr. Behfar Ehdaie: I initially was exposed to medicine in dealing with some of the medical challenges that my mother faced related to cancer. It made a very large impression on me to see how my mother interacted with her physicians and how she was comforted by so many of them. To be able to give back and to provide comfort to other people with regard to different diseases was very important in my decision to be a doctor.

On top of that, being an effective and good physician were challenges that I found to be stimulating.

What is partial-gland ablation versus focal therapy?

Dr. Ehdaie: I think we’ve come to a point in prostate cancer management and treatment in which these distinctions and terminology are becoming more important. As you know, over the past three decades, we have developed proven effective whole-gland treatments for the prostate that include radical surgery and radiation therapy. A less invasive form of prostate cancer treatment must involve less than total treatment of the whole gland. Therefore, the term partial gland has evolved. We use the word ablation to suggest that an area of the prostate will be treated, whether that’s through heating or freezing or other mechanisms to cause cell death and necrosis.

The term focal therapy adds a second dimension to partial-gland ablation. This is a general term to refer to any treatment that offers less than whole-gland treatment for prostate cancer. Focal therapy specifically focuses on an image-guided treatment approach, meaning an area that is visualized is specifically targeted and treated. In partial-gland ablation, we use our current abilities to map the prostate to determine which region is most likely to be involved with cancer; we not only seek to treat that area but also to achieve a margin that may not be visualized on imaging. Focal therapy adds the dimension of image guidance to the armament of prostate cancer treatment, which is more relevant now given that our approach to diagnosing prostate cancer has also evolved over the past decade. We have moved from systematic biopsies to adding biopsies in which we target areas that are first visualized using advanced imaging like multiparametric MRI.

Are you primarily doing focal therapy or partial-gland ablation now?

Dr. Ehdaie: In our different studies and trials, we have different forms of treatment. Specifically, in studies in which we define the area of treatment by MRI, we term those treatments focal therapy. We currently have a clinical trial looking at MR-guided high-intensity focused ultrasound (HIFU) that we perform in the MRI suite. We also have two other clinical trials in which we direct our treatment to a region predominantly defined by the biopsy criteria, in which the imaging is an addition to the tools we have used to define where we want to treat. We currently are performing both focal therapy and partial-gland ablation on patients based on the modalities that they would be eligible for.

How do we know which patients are appropriate for either focal therapy or partial-gland ablation?

Dr. Ehdaie: I think ultimately we can make the distinction between patients who need radical surgery or radiation treatment and those patients who need less invasive forms of treatment that we would term partial-gland ablation specifically, without making the distinction with focal therapy to answer this question.

Currently, I believe eligible patients are those who have an intermediate risk prostate cancer defined as Gleason grade 3+4, or in some cases very low-volume Gleason 4+3 prostate cancer defined by prostate needle biopsy and confirmed with a secondary imaging test to rule out other areas of intermediate-risk prostate cancer. Those patients may have other areas of low-grade, low-risk prostate cancer, specifically Gleason 3+3, which would go untreated and be monitored as they currently are in many active surveillance cohorts. I do not believe focal therapy or partial-gland ablation in its current form should be evaluated or used in patients with high-risk prostate cancer; that includes men with Gleason 4+4 or higher, high-volume Gleason 4+3, with imaging characteristics suggesting bilateral intermediate or high-risk disease, or disease that has escaped the prostate, including locally advanced prostate cancer or prostate cancer that has metastasized to the lymph nodes or the bone.

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Focal Therapy + Imaging

Dr. Mark Emberton is a Professor of Interventional Oncology at University College London.

Prostatepedia spoke with him about focal therapy for prostate cancer.

What is focal therapy for prostate cancer?

IMG_0571Dr. Emberton: Focal therapy is an attempt to improve the therapeutic ratio. It addresses the harms and benefits of treatment. In prostate cancer treatment, the harms are too great for the benefit to accrue.

We can’t improve the benefit very much, but we can certainly reduce the harms that we inflict on our patients. Nearly every patient who has been treated for prostate cancer will experience a reduction in quality of life because of the impact on his sexual function, continence, or rectal function.

Focal therapy attempts to address that by preserving tissue. We’ve managed to preserve tissue in all other cancer management: breast through lumpectomy, kidney through partial nephrectomy, liver through partial hepatectomy, and penile cancer through partial penectomy. Prostate is the last bastion. Until recently, all men had the prostatic equivalent of bilateral mastectomy. In other words, their whole prostate tissue was removed irrespective of tumor volume, location, or number. Everyone was treated the same. With focal therapy, we attempt to preserve tissue, which preserves function.

How do doctors determine if focal therapy is appropriate for a man?

Dr. Emberton: It’s not for everybody. At the moment, we do surveillance so that men with very low-risk disease have no treatment. We offer surgery to men with high-risk disease who’ve got extensive, high-burden tumors in the same way we manage, say, breast cancer. We might choose to watch an elderly woman with a small breast lump. We might choose to do a mastectomy on a young woman with very aggressive breast cancer. But the majority of women—currently 80%—can get away with a lumpectomy. This is enabled by the ability to identify tumors and determine location and volume.

That’s a very recent development in prostate cancer. Until very recently, we were treating all men blindly. Since Hugh Hampton Young did his first prostatectomy at Johns Hopkins about 100 years ago, we’ve been treating prostate cancer without knowledge of tumor location.

What is the role of imaging?

Dr. Emberton: The new trick in town is that we can see the prostate cancer with MRI. If we can see it, we can direct needles at it. If we can direct needles at it, we can direct energy at it. We can zap the tumor rather than having to remove the whole prostate. We can have a much more nuanced approach now. Instead of treating all men the same, we can now stratify men by risk with great precision by biopsying them differently depending on where the tumor is and then allocating treatment depending on the risk stratification that has been assessed. If a man has one millimeter of Gleason 4+3, most of us would not treat. I certainly wouldn’t. If he has extensive bilateral disease, I would offer whole-gland treatment in the form of surgery or radiation therapy. If he has got a 0.5 cc tumor in the right peripheral zone of the prostate, I see no reason why we shouldn’t offer a selective destruction of that tumor that preserves erections, ejaculation, and continence. We’re doing that today. We’re having conversations with men today that we couldn’t have had three to four years ago because we didn’t have the tools.

What about other advances in imaging?

Dr. Emberton: PSMA is very useful in staging men. It’s concordant with MRI and the prostate, but it doesn’t give us the spatial resolution that we would require to decide which part of the prostate to treat. The PSMA PET/CT will be positive on the left or the right side of the prostate, but will not give us any more information. It’s really useful in the high-risk man with whom you’re trying to rule out metastatic disease.

There are a variety of forms of focal therapy, correct?

Dr. Emberton: I think conceptually, it’s very clear. We offer men focal therapy when we can treat the tumor plus a margin and we think we can do so faithfully. But there are lots of ways to do it. Just like surgery, you can have an open, transperineal, laparoscopic, or robotic prostatectomy. In brachytherapy, high-dose rate (HDR), low-dose rate (LDR), CyberKnife, TrueBeam, protons, external beam, the principle is the same.

Yes, we have a few options with focal therapy, though not as many as surgeons and radiation therapists. We’re often accused of having a cornucopia of ways of treating. Actually, we don’t. We have heat (hot or cold) and we have electricity in the form of radio frequency or electroporation.